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Innate Lymphoid Cell Aging

先天性淋巴细胞老化

基本信息

批准号：
10531485
负责人：
Qi yang
金额：
$ 22.38万
依托单位：
RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10531485
关键词：
Innate Lymphoid Cell Aging

项目摘要

Project Summary/Abstract Under this administrative supplement, we propose to examine impact of innate lymphoid cell aging on the disease outcome of SARS-CoV-2 infection, by adding COVID-19 to the parent study which examines the innate lymphoid cell aging during influenza infection. The aged population is particularly susceptible to COVID-19. It is estimated that more than 80% of individuals who have died from COVID-19 in the U.S. are elderly individuals ≥ 65 years old. The underlying mechanisms remain unclear. Aging is associated drastic and complicated changes in the immune system. Aging is associated drastic and complicated changes in the immune system. The mucosal barrier sites harbor unique subsets of innate and innate-like lymphocytes implicated in host defense, tissue homeostasis, and tissue repair. Our published and preliminary data indicate that the long-lived lung-resident innate/innate-like lymphocytes, such as ILC2 and MAIT cells, undergo tremendous changes with aging. We hypothesize that impaired function of mature lung ILC2 underpins tissue damage and inflammation observed during SARS-CoV-2 infection with aging, and that boosting the activity of ILC2 will increase host resistance and tolerance to severe COVID-19 in the elderly individuals. We have recently established a mouse model of SARS-CoV-2 infection in aged mice. We will further characterize this mouse model, and will use this model to test whether enhancing ILC2 activity will increase host resistance and tolerance resistance to COVID-19 in aged mice. We have available for this study a CDC approved full functioning ABSL3 lab. This supplement will directly address multiple objectives related to the goals outlined in the COVID-19 notice of special interest. This supplement will develop aged animal models suitable for studies on pathogenesis of SARS-CoV-2 infection in the aging context. The proposal experiments will also elucidate how cellular and molecular mechanisms of aging impact the treatment, recovery, and repair of tissue and organ systems during SARS-CoV-2 infection.

项目摘要/摘要在这项行政补充下，我们建议检查先天淋巴样细胞的影响。在父母中添加新冠肺炎对SARS-CoV-2感染的疾病结局的影响一项研究流感感染期间先天淋巴细胞老化的研究。老年人人群特别容易受到新冠肺炎的影响。据估计，超过80%的在美国，死于新冠肺炎的人是≥65岁的老年人。这个潜在的机制仍不清楚。老龄化伴随着剧烈而复杂的变化免疫系统。衰老是与免疫系统相关的剧烈而复杂的变化系统。粘膜屏障部位有独特的先天淋巴细胞和先天淋巴细胞亚群。与宿主防御、组织动态平衡和组织修复有关。我们已出版的和初步的数据表明，长期驻留在肺内的先天/先天样淋巴细胞，如ILC2和随着年龄的增长，MAIT细胞会发生巨大的变化。我们假设，功能受损的人成熟的肺ILC2是SARS-CoV-2期间观察到的组织损伤和炎症的基础随着年龄的增长而感染，增强ILC2的活性将增加宿主的抵抗力和老年个体对重度新冠肺炎的耐受性。我们最近培育了一只老鼠老年小鼠SARS-CoV-2感染模型的建立我们将进一步描述这个小鼠模型，并将使用该模型来测试增强ILC2活性是否会增加寄主抗性和老龄小鼠对新冠肺炎的耐受性。我们有一个疾病预防控制中心可用于这项研究获得批准的全功能ABSL3实验室。本附录将直接针对多个目标与新冠肺炎通知中概述的目标相关的特别关注。这份副刊将适合SARS-CoV-2感染发病机制研究的老龄动物模型的建立老龄化的背景。提案实验还将阐明细胞和分子如何衰老机制影响组织和器官系统的治疗、恢复和修复在SARS-CoV-2感染期间。